Bioinspired Suspended Sensing Membrane Array with Modulable Wedged-Conductive Channels for Crosstalk-Free and High-Resolution Detection.

High spatial-resolution detection is essential for biomedical applications and human-machine interaction. However, as the sensor array density increases, the miniaturization will lead to interference between adjacent units and deterioration in sensing performance. Here, inspired by the cochlea's sensing structure, a high-density flexible pressure sensor array featuring with suspended sensing membrane with sensitivity-enhanced customized channels is presented for crosstalk-free and high-resolution detection. By imitating the basilar membrane attached to spiral ligaments, a sensing membrane is fixed onto a high-stiffness substrate with cavities, forming a stable braced isolation to provide an excellent crosstalk-free capability (crosstalk coefficient: 47.24 dB) with high-density integration (100 units within 1 cm2). Similar to the opening of ion channels in hair cells, the wedge-type expansion of the embedded cracks introduced by stress concentration structures enables a high sensitivity (0.19 kPa-1) and a large measuring range (400 kPa). Finally, it demonstrates promising applications in distributed displays and the condition monitoring of medical-surgical intubation.

Design and demonstration of high efficiency perfectly vertical grating couplers with a random structure.

Utilizing an automated optimization method, we propose a perfectly vertical grating coupler (PVGC) characterized by random structure, superior performance, simplified fabrication process, and increased minimum feature size (MFS). Within the range of MFS from 60 to 180 nm, the optimized PVGC exhibited a simulated coupling efficiency of approximately -2.0 dB at 1550 nm with a 34 nm 1-dB bandwidth. Experimental results for the PVGCs fabricated by electron beam lithography (EBL) demonstrated coupling efficiencies ranging from -2.5 to -2.8 dB with a 32 nm 1-dB bandwidth while maintaining high manufacturing tolerances. This represents the most outstanding experimental outcome to date regarding the coupling performance of a PVGC fabricated on a 220 nm silicon on insulator (SOI), without requiring any complex processes as reported in the existing literature.

Structural insights into vesicular monoamine storage and drug interactions.

Biogenic monoamines-vital transmitters orchestrating neurological, endocrinal and immunological functions1-5-are stored in secretory vesicles by vesicular monoamine transporters (VMATs) for controlled quantal release6,7. Harnessing proton antiport, VMATs enrich monoamines around 10,000-fold and sequester neurotoxicants to protect neurons8-10. VMATs are targeted by an arsenal of therapeutic drugs and imaging agents to treat and monitor neurodegenerative disorders, hypertension and drug addiction1,8,11-16. However, the structural mechanisms underlying these actions remain unclear. Here we report eight cryo-electron microscopy structures of human VMAT1 in unbound form and in complex with four monoamines (dopamine, noradrenaline, serotonin and histamine), the Parkinsonism-inducing MPP+, the psychostimulant amphetamine and the antihypertensive drug reserpine. Reserpine binding captures a cytoplasmic-open conformation, whereas the other structures show a lumenal-open conformation stabilized by extensive gating interactions. The favoured transition to this lumenal-open state contributes to monoamine accumulation, while protonation facilitates the cytoplasmic-open transition and concurrently prevents monoamine binding to avoid unintended depletion. Monoamines and neurotoxicants share a binding pocket that possesses polar sites for specificity and a wrist-and-fist shape for versatility. Variations in this pocket explain substrate preferences across the SLC18 family. Overall, these structural insights and supporting functional studies elucidate the mechanism of vesicular monoamine transport and provide the basis to develop therapeutics for neurodegenerative diseases and substance abuse.

Exploration of Directing-Group-Assisted, Copper-Mediated Radiofluorination and Radiosynthesis of [18F]Olaparib.

Copper-mediated radiofluorination (CMRF) of organoboronic precursors is the method of choice for late-stage radiofluorination of aromatic compounds as positron emission tomography (PET) radiotracers. However, CMRF generally requires harsh reaction conditions, a large amount of substrates, and harsh solvents (e.g., DMA) to proceed, affording variable radiochemical yields (RCYs). Using [18F]tosyl fluoride as the source of [18F]fluoride, we have found a highly efficient CMRF of organoboronic precursors, assisted by a directing group (DG) at the ortho position. The reaction can be carried out under mild conditions (even at room temperature) in acetonitrile and results in high RCYs, providing a novel strategy for the radiofluorination of aromatic compounds. The exploration of this strategy also provided more information about side reactions in CMRF. Using this strategy, [18F]olaparib has been radiosynthesized in high RCYs, with high molar activity and high chemical and radiochemical purities, demonstrating the great potential of DG-assisted CMRF in the preparation of 18F-labeled PET radiotracers.

Single-use flexible ureteroscope provides an alternative treatment for upper urinary calculi: A systematic review and meta-analysis.

OBJECTIVE: This study aimed to evaluate the efficacy and safety of single-use flexible ureteroscope and reusable flexible ureteroscope for upper urinary calculi. METHODS: We conducted a meta-analysis that had a comprehensive search in PubMed, Embase, Cochrane Library, Web of Science, and WanFang databases from 2000/01/01 to 2023/06/01 for available randomized controlled trials. "Ureteroscopes," "Flexible Ureteroscope," "Single-use," and "Upper Urinary Calculi" were used as the major keywords for the search. Review Manager 5.0 and STATA 12.0 were used for calculation and statistical analysis. RESULTS: A total of 9 randomized controlled trials comprising 1293 participants were included in our meta-analysis. Single use-FURS had better results in stone-free rate (relative risk: 1.08, 95% confidence interval: [1.02, 1.15], P = .02) and postoperative infection (relative risk: 0.41, 95% confidence interval: [0.23, 0.72], P = .002). Operative time, hemoglobin decline, postoperative serum creatinine, postoperative hospital stay, and overall complication after surgery showed no significant differences between the 2 procedures (P > .05). CONCLUSION: Single-use flexible ureteroscope provides a valuable alternative to reusable flexible ureteroscope in upper urinary calculi with its better visual field performance and manipulation, opening a new technological revolution for kidney stone treatment.

A practical protocol for large-scale copper-mediated radioiodination of organoboronic precursors: Radiosynthesis of [123 I]KX-1 for Auger radiotherapy.

Nucleophilic copper-mediated radioiodination (CMRI) of organoboronic precursors with radioiodides is a promising method of radioiodination. The previously reported CMRI has demonstrated its great potential and scope of labeling for the radiosynthesis of radioiodine-labeled compounds. However, the reported protocols (using a small amount/volume of radioactivity) are practically not reproducible in large-scale CMRI, in which the radioactivity was usually provided in a bulk alkaline solution. A large amount of water and a strong base are incompatible with CMRI. To overcome these issues in large-scale CMRI, we have developed a simple protocol for large-scale CMRI. The bulk water was removed under a flow of inert gas at 110°C, and the strong base (i.e., NaOH) was neutralized with an acid, pyridinium p-toluenesulfonate or p-toluenesulfonic acid. In the model reactions of [123 I]KX-1, a PARP-1 radioligand for Auger radiotherapy, radiochemical conversions were significantly improved after neutralization of the base, and the addition of additional acids was tolerated and favorable for the reactions. Using this protocol, [123 I]KX-1 was radiosynthesized from 20 mCi (0.74 GBq) of [123 I]iodide in high radiochemical yields, high radiochemical purity, and high molar activity. This protocol should be applicable to the radiosynthesis of other compounds with radioiodine via CMRI.

Tyrosine Kinase Inhibitors for Renal Cell Carcinoma: A Bibliometric Analysis via CiteSpace from 2000 to 2022.

BACKGROUND: The aim of the study was to identify the cooperation of authors, countries, institutions and explore the hot spots regarding research of tyrosine kinase inhibitors (TKIs) for renal cell carcinoma (RCC) treatment in the past 22 years. SUMMARY: Relevant original and review articles were obtained from the Web of Science Core Collection from 2000 to 2022. CiteSpace software was used to perform the visualization of scientific productivity and emerging trends. Network maps were generated to evaluate the collaborations between different authors, countries, institutions, and keywords. KEY MESSAGES: A total of 4,951 articles related to TKI for RCC treatment were identified. We observed a gradual increase in the number of publications from 2000 to 2022. The USA dominated the field in all countries, and Mem Sloan Kettering Cancer Centre (USA) had more extensive cooperating relationships with other institutions. Motzer RJ and Escudier B were two of the authority scholars in this specific field with the most publications and co-citations. Journal of Clinical Oncology had the most citations of all the journals. A total of 10 major clusters were explored based on the reference co-citation analysis. From 2000 to 2022, the research hot spots have undergone two dramatic shifts during 2006 and 2019, respectively, relevant topics were TKI and TKI combined with immune checkpoint inhibitors (CPIs). At present, the research hot spots focus on CPI and targeted therapies. Bibliometric analysis is allowing researchers to recognize the current research status by providing a comprehensive overview of the development of scientific literature related to TKI for RCC treatment, and information for further research be demonstrated as well.

Ibrutinib Inhibits BTK Signaling in Tumor-Infiltrated B Cells and Amplifies Antitumor Immunity by PD-1 Checkpoint Blockade for Metastatic Prostate Cancer.

Metastatic prostate cancer (PCa) remains incurable and causes considerably diminished overall survival. Despite significant progress in pharmacotherapy, the disease prognosis remains unchanged. Immune checkpoint inhibitors (ICIs) have demonstrated effectiveness in treating various advanced malignancies, but their efficacy in metastatic PCa is relatively limited. Previous studies have confirmed the immunosuppressive role of tumor-infiltrating B cells (TIL-Bs) in the PCa microenvironment, which accounts for their poor immunogenic potency. In this study, we demonstrated that an oral kinase agent, ibrutinib, strongly potentiated anti-PD-1 checkpoint blockade efficacy and successfully controlled tumor growth in a murine orthotopic PCa model constructed using a metastatic and hormone-independent cell line (RM-1). We identified close relationships between TIL-Bs, Bruton's tyrosine kinase (BTK), and immunosuppressive molecules by bioinformatics and histological analysis. An in vitro study showed that a low dose of ibrutinib significantly inhibited B cell proliferation and activation as well as IL-10 production through the BTK pathway. Moreover, ibrutinib-treated B cells promoted CD8+ T cell proliferation and inhibitory receptor (IR) expression. However, the same dose of ibrutinib was insufficient to induce apoptosis in cancer cells. An in vivo study showed that ibrutinib monotherapy failed to achieve tumor regression in murine models but decreased B cell infiltration and inhibited activation and IL-10 production. More importantly, CD8+ T cell infiltration increased with high IR expression. Ibrutinib synergized with anti-PD-1 checkpoint blockade enormously improved antitumor immunity, thereby reducing tumor volume in the same scenario. These data set the scene for the clinical development of ibrutinib as an immunogenic trigger to potentiate anti-PD-1 checkpoint blockade for metastatic PCa immunotherapy.

Human striatal glia differentially contribute to AD- and PD-specific neurodegeneration.

The commonalities and differences in cell-type-specific pathways that lead to Alzheimer disease (AD) and Parkinson disease (PD) remain unknown. Here, we performed a single-nucleus transcriptome comparison of control, AD and PD striata. We describe three astrocyte subpopulations shared across different brain regions and evolutionarily conserved between humans and mice. We reveal common features between AD and PD astrocytes and regional differences that contribute toward amyloid pathology and neurodegeneration. In contrast, we found that transcriptomic changes in microglia are largely unique to each disorder. Our analysis identified a population of activated microglia that shared molecular signatures with murine disease-associated microglia (DAM) as well as disease-associated and regional differences in microglia transcriptomic changes linking microglia to disease-specific amyloid pathology, tauopathy and neuronal death. Finally, we delineate undescribed subpopulations of medium spiny neurons (MSNs) in the striatum and provide neuronal transcriptomic profiles suggesting disease-specific changes and selective neuronal vulnerability.

[18F]Tosyl fluoride as a versatile [18F]fluoride source for the preparation of 18F-labeled radiopharmaceuticals.

Positron emission tomography (PET) is an in vivo imaging technology that utilizes positron-emitting radioisotope-labeled compounds as PET radiotracers that are commonly used in clinic and in various research areas, including oncology, cardiology, and neurology. Fluorine-18 is the most widely used PET-radionuclide and commonly produced by proton bombardment of 18O-enriched water in a cyclotron. The [18F]fluoride thus obtained generally requires processing by azeotropic drying in order to completely remove H2O before it can be used for nucleophilic radiofluorination. In general, the drying step is important in facilitating the radiofluorination reactions and the preparation of 18F-labeled PET radiotracers. In this communication, we have demonstrated the feasibility of using [18F]tosyl fluoride ([18F]TsF) as a versatile [18F]fluoride source for radiofluorination to bypass the azeotropic drying step, and we have developed a continuous flow solid-phase radiosynthesis strategy to generate [18F]TsF in a form that is excellent for radiofluorination. [18F]TsF shows high reactivity in radiofluorination and provides the features suitable for preparing PET radiotracers on a small scale and exploring novel radiolabeling technologies. Thus, using [18F]TsF as a [18F]fluoride source is a promising strategy that facilitates radiofluorination and provides a convenient and efficient solution for the preparation of 18F-labeled radiopharmaceuticals that is well matched to the emerging trends in PET imaging technologies.

Preclinical Efficacy of a PARP-1 Targeted Auger-Emitting Radionuclide in Prostate Cancer.

There is an unmet need for better therapeutic strategies for advanced prostate cancer. Poly (ADP-ribose) polymerase-1 (PARP-1) is a chromatin-binding DNA repair enzyme overexpressed in prostate cancer. This study evaluates whether PARP-1, on account of its proximity to the cell's DNA, would be a good target for delivering high-linear energy transfer Auger radiation to induce lethal DNA damage in prostate cancer cells. We analyzed the correlation between PARP-1 expression and Gleason score in a prostate cancer tissue microarray. A radio-brominated Auger emitting inhibitor ([77Br]Br-WC-DZ) targeting PARP-1 was synthesized. The ability of [77Br]Br-WC-DZ to induce cytotoxicity and DNA damage was assessed in vitro. The antitumor efficacy of [77Br]Br-WC-DZ was investigated in prostate cancer xenograft models. PARP-1 expression was found to be positively correlated with the Gleason score, thus making it an attractive target for Auger therapy in advanced diseases. The Auger emitter, [77Br]Br-WC-DZ, induced DNA damage, G2-M cell cycle phase arrest, and cytotoxicity in PC-3 and IGR-CaP1 prostate cancer cells. A single dose of [77Br]Br-WC-DZ inhibited the growth of prostate cancer xenografts and improved the survival of tumor-bearing mice. Our studies establish the fact that PARP-1 targeting Auger emitters could have therapeutic implications in advanced prostate cancer and provides a strong rationale for future clinical investigation.

Identification and Characterization of ML321: A Novel and Highly Selective D2 Dopamine Receptor Antagonist with Efficacy in Animal Models That Predict Atypical Antipsychotic Activity.

We have developed and characterized a novel D2R antagonist with exceptional GPCR selectivity - ML321. In functional profiling screens of 168 different GPCRs, ML321 showed little activity beyond potent inhibition of the D2R and to a lesser extent the D3R, demonstrating excellent receptor selectivity. The D2R selectivity of ML321 may be related to the fact that, unlike other monoaminergic ligands, ML321 lacks a positively charged amine group and adopts a unique binding pose within the orthosteric binding site of the D2R. PET imaging studies in non-human primates demonstrated that ML321 penetrates the CNS and occupies the D2R in a dose-dependent manner. Behavioral paradigms in rats demonstrate that ML321 can selectively antagonize a D2R-mediated response (hypothermia) while not affecting a D3R-mediated response (yawning) using the same dose of drug, thus indicating exceptional in vivo selectivity. We also investigated the effects of ML321 in animal models that are predictive of antipsychotic efficacy in humans. We found that ML321 attenuates both amphetamine- and phencyclidine-induced locomotor activity and restored pre-pulse inhibition (PPI) of acoustic startle in a dose-dependent manner. Surprisingly, using doses that were maximally effective in both the locomotor and PPI studies, ML321 was relatively ineffective in promoting catalepsy. Kinetic studies revealed that ML321 exhibits slow-on and fast-off receptor binding rates, similar to those observed with atypical antipsychotics with reduced extrapyramidal side effects. Taken together, these observations suggest that ML321, or a derivative thereof, may exhibit ″atypical″ antipsychotic activity in humans with significantly fewer side effects than observed with the currently FDA-approved D2R antagonists.

A Scientometric Visualization Analysis for Benign Prostatic Hyperplasia from 2016 to 2022.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common urological disorder leading to dysuria in middle-aged and elderly men and significantly reduces the quality of life of patients. Technology for BPH has made a great progress, while there is still a lack of visual and summary literature to make the summary. SUMMARY: The aims of the study were to identify the cooperation of authors, countries, institutions, and explore hot topics' prospects regarding research of BPH. Relevant original articles were obtained from the Web of Science (WoS) database between 2016 and 2022. CiteSpace software was used to perform the analysis and visualization of scientific productivity and emerging trends. KEY MESSAGES: A total of 4,738 articles related to study of BPH were identified. We observed a gradual increase in the number of publications from 2016 to 2022. The USA dominated the field in all countries. Shanghai Jiao Tong University was the most productive institution in 6 years. Active cooperation between countries and between institutions was not observed. Journal of Urology was the most co-cited journal. Roehrborn CG (41 papers) was the most productive author and had the largest numbers of citations (820 co-citations) during the past 6 years. Close collaboration was not observed between the different authors. The main hot topics included matters related to BPH, urinary tract symptom, prostatic urethral lift, thermal therapy, and prostatic neoplasms. This scientometric study comprehensively reviewed publications related to BPH during the past 6 years using quantitative and qualitative methods, which can be used to forecast future research developments in BPH.

Dopamine D3 Receptor in Parkinson Disease: A Prognosis Biomarker and an Intervention Target.

Parkinson disease (PD) dementia, pathologically featured as nigrostriatal dopamine (DA) neuronal loss with motor and non-motor manifestations, leads to substantial disability and economic burden. DA therapy targets the DA D3 receptor (D3R) with high affinity and selectivity. The pathological involvement of D3R is evidenced as an effective biomarker for disease progression and DA agnostic interventions, with compensations of increased DA, decreased aggregates of α-synuclein (α-Syn), enhanced secretion of brain-derived neurotrophic factors (BDNF), attenuation of neuroinflammation and oxidative damage, and promoting neurogenesis in the brain. D3R also interacts with D1R to reduce PD-associated motor symptoms and alleviate the side effects of levodopa (L-DOPA) treatment. We recently found that DA D2 receptor (D2R) density decreases in the late-stage PDs, while high D3R or DA D1 receptor (D1R) + D3R densities in the postmortem PD brains correlate with survival advantages. These new essential findings warrant renewed investigations into the understanding of D3R neuron populations and their cross-sectional and longitudinal regulations in PD progression.

Solid phase radiosynthesis of an olaparib derivative using 4-[18F] fluorobenzoic acid and in vivo evaluation in breast and prostate cancer xenograft models for PARP-1 expression.

INTRODUCTION: Solid-phase synthesis and conjugation reactions of acids and amines using coupling reagents are common in organic synthesis, but rare in 18F radiochemistry. 4-[18F]Fluorobenzoic acid (FBA) is a useful building block, but is seldom used directly with coupling reagents for the preparation of 18F radiopharmaceuticals. To overcome the inconveniences associated with using [18F]FBA in conjugation reactions, we have developed a non-covalent solid-phase synthesis (SPS) strategy for the radiosynthesis of [18F]PARPi, a derivative of olaparib as a Poly (ADP-ribose) polymerase-1 (PARP-1) radioligand. METHODS: Fluoro-, bromo- and iodo-benzoic derivatives of olaparib were synthesized, and their PARP-1 affinities were measured using a recently developed cell culture-based competitive assay. To produce [18F]PARPi, [18F]FBA was radiosynthesized and purified using a cation-exchange cartridge, and then trapped by an anion-exchange resin cartridge, on which the solid-phase radiosynthesis was carried out to produce the desired product. [18F]PARPi was evaluated in vivo in breast and prostate xenograft tumor models by microPET imaging, biodistribution and autoradiography. RESULTS: The best derivatives of olaparib were identified as compound 4, 7 and 8. [18F]4 ([18F]PARPi) was radiosynthesized in high radiochemical yield, high molar activity and high radiochemical purity using this SPS strategy. The in vivo evaluation of [18F]PARPi demonstrates the PARP-1 specific uptake of [18F]PARPi in the animal models. CONCLUSIONS: This method is simple and efficient, having great potential for the synthesis of radiopharmaceuticals starting from [18F]FBA or other radiolabeled aromatic acids. Using [18F]PARPi prepared by this method, we demonstrated the promise of [18F]PARPi in the nuclear imaging of PARP-1 expression.

Striatal oxidative damages and neuroinflammation correlate with progression and survival of Lewy body and Alzheimer diseases.

Neurodegenerative diseases are a class of chronic and complex disorders featuring progressive loss of neurons in distinct brain areas. The mechanisms responsible for the disease progression in neurodegeneration are not fully illustrated. In this observational study, we have examined diverse biochemical parameters in the caudate and putamen of patients with Lewy body diseases (LBDs) and Alzheimer disease (AD), shedding some light on the involvement of oxidative damage and neuroinflammation in advanced neurodegeneration. We performed Spearman and Mantel-Cox analyses to investigate how oxidative stress and neuroinflammation exert comprehensive effects on disease progression and survival. Disease progression in LBDs correlated positively with poly (ADP-Ribose) and triggering receptors expressed on myeloid cell 2 levels in the striatum of LBD cohorts, indicating that potential parthanatos was a dominant feature of worsening disease progression and might contribute to switching microglial inflammatory phenotypes. Disease progression in AD corresponds negatively with 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) and myeloperoxidase concentrations in the striatum, suggesting that possible mitochondria dysfunction may be involved in the progression of AD via a mechanism of ß-amyloid entering the mitochondria and subsequent free radicals generation. Patients with lower striatal 8-oxo-dG and myeloperoxidase levels had a survival advantage in AD. The age of onset also affected disease progression. Tissue requests for the postmortem biochemistry, genetics, and autoradiography studies were approved by the Washington University Alzheimer's Disease Research Center (ADRC) Biospecimens Committee (ethics approval reference number: T1705, approval date: August 6, 2019). Recombinant DNA and Hazardous Research Materials were approved by the Washington University Environmental Health & Safety Biological Safety Committee (approval code: 3739, approval date: February 25, 2020). Radioactive Material Authorization was approved by the Washington University Environmental Health & Safety Radiation Safety Committee (approval code: 1056, approval date: September 18, 2019).

Neuropathic Pain: Biomolecular Intervention and Imaging via Targeting Microglia Activation.

Many diseases, including cancer, can lead to neuropathic pain (NP). NP is one of the accompanying symptoms of suffering in many conditions and the life quality of NP patient is seriously affected. Due to complex causes, the effects of clinical treatments have been very unsatisfactory. Many experts have found that neuron-microglia interaction plays an essential role in NP occurrence and development. Therefore, the activation of microglia, related inflammatory mediators and molecular and cellular signaling pathways have become the focus of NP research. With the help of modern functional imaging technology, advanced pre-and clinical studies have been carried out and NP interventions have been attempted by using the different pharmaceuticals and the extracted active components of various traditional herbal medicines. In this communication, we review the mechanism of microglia on NP formation and treatment and molecular imaging technology's role in the clinical diagnosis and evaluation of NP therapies.

Radiosynthesis and Evaluation of Talazoparib and Its Derivatives as PARP-1-Targeting Agents.

Poly (ADP-ribose) polymerase-1 (PARP-1) is a critical enzyme in the DNA repair process and the target of several FDA-approved inhibitors. Several of these inhibitors have been radiolabeled for non-invasive imaging of PARP-1 expression or targeted radiotherapy of PARP-1 expressing tumors. In particular, derivatives of olaparib and rucaparib, which have reduced trapping potency by PARP-1 compared to talazoparib, have been radiolabeled for these purposes. Here, we report the first radiosynthesis of [18F]talazoparib and its in vitro and in vivo evaluation. Talazoparib (3a″) and its bromo- or iodo-derivatives were synthesized as racemic mixtures (3a, 3b and 3c), and these compounds exhibit high affinity to PARP-1 (Ki for talazoparib (3a″): 0.65 ± 0.07 nM; 3a: 2.37 ± 0.56 nM; 3b: 1.92 ± 0.41 nM; 3c: 1.73 ± 0.43 nM; known PARP-1 inhibitor Olaparib: 1.87 ± 0.10 nM; non-PARP-1 compound Raclopride: >20,000 nM) in a competitive binding assay using a tritium-labeled PARP-1 radioligand [3H]WC-DZ for screening. [18F]Talazoparib (3a″) was radiosynthesized via a multiple-step procedure with good radiochemical and chiral purities (98%) and high molar activity (28 GBq/µmol). The preliminary biodistribution studies in the murine PC-3 tumor model showed that [18F]talazoparib had a good level of tumor uptake that persisted for over 8 h (3.78 ± 0.55 %ID/gram at 4 h and 4.52 ± 0.32 %ID/gram at 8 h). These studies show the potential for the bromo- and iodo- derivatives for PARP-1 targeted radiotherapy studies using therapeutic radionuclides.

Dopamine D1 + D3 receptor density may correlate with parkinson disease clinical features.

OBJECTIVE: Dopamine D2-like receptors - mainly dopamine D2 receptors (D2R) and dopamine D3 receptors (D3R) - are believed to be greatly involved in the pathology of Parkinson disease (PD) progression. However, these receptors have not been precisely examined in PD patients. Our aim was to quantitatively calculate the exact densities of dopamine D1 receptors (D1R), D2R, and D3R in control, Alzheimer disease (AD), and Lewy body disease (LBD) patients (including PD, Dementia with Lewy bodies, and Parkinson disease dementia); and analyze the relationship between dopamine receptors and clinical PD manifestations. METHODS: We analyzed the densities of D1R, D2R, and D3R in the striatum and substantia nigra (SN) using a novel quantitative autoradiography procedure previously developed by our group. We also examined the expression of D2R and D3R mRNA in the striatum by in situ hybridization. RESULTS: The results showed that although no differences of striatal D1R were found among all groups; D2R was significantly decreased in the striatum of PD patients when compared with control and AD patients. Some clinical manifestations: age of onset, PD stage, dopamine responsiveness, and survival time after onset; showed a better correlation with striatal D1R + D3R densities combined compared to D1R or D3R alone. INTERPRETATION: There is a possibility that we may infer the results in diagnosis, treatment, and prognosis of PD by detecting D1R + D3R as opposed to using dopamine D1 or D3 receptors alone. This is especially true for elderly patients with low D2R expression as is common in this disease.